A research team led by scientists at AIDS Institute and Department
of Microbiology, Li Ka Shing Faculty of Medicine of The University of Hong Kong
(HKU) invents a universal antibody
drug against HIV/AIDS. By engineering a tandem bi-specific broadly neutralizing
antibody, the team found that this novel antibody
drug is universally effective not only against all genetically divergent
global HIV-1 strains tested but also promoting the elimination of latently
infected cells in a humanized mouse model. The new findings are now published
in the April issue of Journal of
Clinical Investigation.
AIDS remains an incurable disease. In the world, HIV/AIDS has resulted in
estimated 40 million deaths while 36.9 million people are still living with the
virus. To end the HIV/AIDS pandemic, it is important to discover either an
effective vaccine or a therapeutic cure. There are, however, two major
scientific challenges: the tremendous HIV-1 diversity and the
antiviral drug-unreachable latency. Since it is extremely difficult to develop
an appropriate immunogen to elicit broadly neutralizing antibodies (bnAbs)
against genetically divergent HIV-1 subtypes, developing existing bnAbs as
passive immunization becomes a useful approach for HIV-1
prophylaxis and immunotherapy.
Previous studies have investigated the potency, breadth and crystal
structure of many bnAbs including their combination both in vitro and in vivo.
Naturally occurring HIV-1
resistant strains, however, are readily found against these so-called bnAbs and
result in the failure of durable viral suppression in bnAb-based monotherapy.
To improve HIV-1 neutralization breadth and potency, bispecific
bnAb, which blocks two essential steps of HIV-1 entry into target cells,
have been engineered and show promising efficacy in animal models. Before the
publication, tandem bi-specific bnAb has not been previously investigated in
vivo against HIV-1
infection.
Research method and findings
The HKU research team invented a single gene-encoded tandem broadly
neutralizing antibody, titled "BiIA-SG,"
which "kills two birds with one stone." By attaching to host protein
CD4, BiIA-SG strategically ambushes invading HIV-1 particles to protect CD4
positive T cells. BiIA-SG not only displays a potent activity against all three
panels of 124 genetically divergent global HIV-1 strains tested, but also
prevents diverse live viral challenges completely in humanized mice. Moreover,
gene transfer of BiIA-SG
achieves pro-longed drug availability in vivo, leading to a promising efficacy
of eliminating HIV-1 infected cells in humanized mice. Therefore, the research
team provides a proof-of-concept that BiIA-SG is a novel universal antibody
drug for prevention and immunotherapy
against HIV-1 infection.
Significance of the study
The accumulated number of HIV-1
infections has more than doubled from 4,443 diagnostic cases in 2009 to 9,091
in 2017, despite the timely introduced combination antiretroviral therapy and
prevention interventions in Hong Kong. Currently, the estimated annual cost is
over HK$550 millions for antiretroviral
drugs alone per year in Hong Kong, not to mention the rising issues of
life-long financial burdens, drug toxicity and resistant viruses. The newly
invented universal antibody drug brings the hope to fight these issues. With
significantly improved breadth and potency, BiIA-SG
will hopefully be the first "Made in Hong Kong" anti-HIV-1 antibody
drug for clinical development.
To present your research paper in front of the experts from around the globe,
under the Session: Treatment Strategies, Sub-Track: Immunotherapy submit your
abstracts here: https://std-hiv-aids.cmesociety.com/call-for-abstracts/treatment-strategies
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